A Treatment Legacy Effect of Metformin in Obese Women With PCOS

A Treatment Legacy Effect of Metformin on Metabolic and Endocrine Parameters in Obese Women With Polycystic Ovary Syndrome (PCOS)

Metformin has multiple health promoting effects and it may serve as a preventive measure for individuals who are at high risk for metabolic complications.

According to the latest international guidelines it should be considered as an adjunct therapy to lifestyle intervention in all overweight/obese women with PCOS, independently of their glucose homeostasis and menstrual regularity. However, there is no clear answer for how long metformin should be prescribed in this subset of women with PCOS and for how long the beneficial impact would sustain after treatment cessation.

The investigators compared the consequences of metformin withdrawal after long-term therapy as opposed to the consequences of metformin suspension after short term therapy in overweight/obese women with PCOS that had previously responded to metformin by means of moderate weight loss, improved menstrual frequency and sustained normal glucose homeostasis.

Study Overview

• Status: Completed
• Conditions: PCOS
• Intervention / Treatment: Drug: Metformin

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Center Ljubljana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

The investigators conducted 20 obese women with PCOS with normal glucose homeostasis (without known type 1 or type 2 diabetes mellitus) who have been treated with metformin for one year prior to the study and 20 obese women with PCOS with normal glucose homeostasis (without known type 1 or type 2 diabetes mellitus) who have been treated with metformin for at least three years prior to the study.

Description

Inclusion Criteria:

• PCOS defined by the National Institute of Child Health and Human Development (NICHD) criteria
• obesity with body mass index ≥ 30 kg/m2
• normal glucose homeostasis at metformin treatment

Exclusion Criteria:

• known type 1 or type 2 diabetes mellitus
• heart failure
• renal insufficiency with serum creatinine more than 125 umol/L
• arterial hypertension
• pregnancy
• BMI below 25 kg/m2

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; Obese women who have been treated with metformin for one year prior to the study.	Drug: Metformin; metformin cessation
Group B; Obese women who have been treated with metformin for at least three years prior to the study.	Drug: Metformin; metformin cessation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main outcome was change in body weight.		Patient's body weight was measured at the base point and at the endpoint of 6 months of clinical trial.
The main outcome was change in insulin resistance measured with homeostasis model assessment (HOMA IR).	HOMA IR was calculated as the product of the fasting glucose and insulin concentration divided by 22.5.	HOMA IR was calculated at the base point and at the endpoint of 6 months of clinical trial.
The main outcome was change in expression of glucose transporter type 4 (GLUT-4) in adipose tissue.	We obtained adipose tissue using needle biopsy, from which we isolated ribonucleic acid and after reverse transcription, real-time quantitative polymerase chain reaction determined messenger ribonucleic acid expression for GLUT-4.	We did adipose tissue needle biopsy at the base point and at the endpoint of 6 months of clinical trial. All samples were frozen and then analysed together after end point of the study.

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana

Publications and helpful links

General Publications

• Kravos NA, Janez A, Goricar K, Dolzan V, Jensterle M. Effects of metformin withdrawal after long and short term treatment in PCOS: observational longitudinal study. Diabetol Metab Syndr. 2021 Apr 12;13(1):43. doi: 10.1186/s13098-021-00660-5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 25, 2019
• Primary Completion (ACTUAL): December 4, 2019
• Study Completion (ACTUAL): February 1, 2020

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (ACTUAL): September 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: obesity; PCOS; metformin
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: MET prosp

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No